We have described a specific, sensitive radioimmunoassay (RIA) for myelin basic protein (Cohen et al., J. Neurochem. 25: 371, 1975). This assay has been applied to cerebrospinal fluid (CSF) of multiple sclerosis patients. The myelin basic protein is present in multiple sclerosis patiets with acute exacerbation, and during the demyelinative attack, high levels of myelin basic protein are found (10-50 ng/ml). Myelin basic protein is absent from the cerebrospinal fluid of patients wit nondemeyelinative neurologic disease and multiple sclerosis patients in remission. Thus, radioimmunoasay of myelin basic protein in cerebrospinal fluid is a useful test for active demyelination (Cohen et al., New Engl. J. Med. 295: 1455, 1976). These findings are being extended to identify the exact properties of the basic protein in spinal fluid (i.e., whether it is membrane-bound, present as peptide fragments, associated with lipids or ther proteins, etc.). To accomplish this, immunochemical and molecular filtration methods are used. In addition, we are determining if these properties change during a demyelinative attack. Optic neuritis patients are being followed for several years to determine if their initial CSF basic protein (30% of optic neuritis paients looked at to date have CSF basic protein) correlates with the outcome of their illness. In addition, these studies have been extended to include leukemia patients with encephalopathies and myelinopathies where myelin breakdown may occur due to chemotherapy. Myelination is also being investigated using immunochemical probes such as RIA, immunoprecipitation and immunoperoxidase localization to study basic protein synthesis and myelin function in normal and mutant mouse brain. Questions such as the cellular sites and mechanism of myelin synthesis in normal and pathological brain are being addressed.